Wells Maeve, Steiner Laurie
Department of Pediatrics, University of Rochester, Rochester, NY, United States.
Front Genet. 2022 Mar 7;13:805265. doi: 10.3389/fgene.2022.805265. eCollection 2022.
Erythropoiesis is a process of enormous magnitude, with the average person generating two to three million red cells every second. Erythroid progenitors start as large cells with large nuclei, and over the course of three to four cell divisions they undergo a dramatic decrease in cell size accompanied by profound nuclear condensation, which culminates in enucleation. As maturing erythroblasts are undergoing these dramatic phenotypic changes, they accumulate hemoglobin and express high levels of other erythroid-specific genes, while silencing much of the non-erythroid transcriptome. These phenotypic and gene expression changes are associated with distinct changes in the chromatin landscape, and require close coordination between transcription factors and epigenetic regulators, as well as precise regulation of RNA polymerase II activity. Disruption of these processes are associated with inherited anemias and myelodysplastic syndromes. Here, we review the epigenetic mechanisms that govern terminal erythroid maturation, and their role in human disease.
红细胞生成是一个规模巨大的过程，普通人每秒会生成两到三百万个红细胞。红系祖细胞起始为具有大细胞核的大细胞，在三到四次细胞分裂过程中，它们的细胞大小会急剧减小，同时伴随着细胞核的深度浓缩，最终导致去核。随着成熟的成红细胞经历这些显著的表型变化，它们会积累血红蛋白并表达高水平的其他红系特异性基因，同时使大部分非红系转录组沉默。这些表型和基因表达的变化与染色质景观的明显变化相关，并且需要转录因子和表观遗传调节因子之间的密切协调，以及RNA聚合酶II活性的精确调节。这些过程的破坏与遗传性贫血和骨髓增生异常综合征有关。在这里，我们综述了控制红系终末成熟的表观遗传机制及其在人类疾病中的作用。
